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1.
Int Braz J Urol ; 47(1): 159-168, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33047921

RESUMO

PURPOSE: Epidemiological studies reported conflicting results about preoperative hydronephrosis in upper tract urothelial carcinoma (UTUC). This study aimed to investigate the association between preoperative hydronephrosis and pathologic features and oncologic outcomes in patients with UTUC treated by radical nephroureterectomy (RNU). MATERIALS AND METHODS: This was a retrospective, single-center cohort study of 377 patients treated by RNU without perioperative chemotherapy between January 2001 and December 2014. Logistic regression, Cox regression, and survival analyses were performed. RESULTS: Among the 226 patients with high-grade UTUC, 132 (58%) had preoperative hydronephrosis. Multivariable logistic regression revealed that hydronephrosis was independently associated with advanced pT stage (P=0.017) and lymph node or lymphovascular invasion (P=0.002). Median follow-up was 36 months (interquartile range: 20-48 months). The 3- and 5-year overall survival (OS) rates in patients with hydronephrosis were significantly lower than in those without hydronephrosis (both P <0.001). The 3- and 5-year cancer-specific survival (CSS) rates in patients with hydronephrosis were significantly lower than in those without hydronephrosis (both P=0.001). Hydronephrosis was independently associated with OS and CSS (P=0.001 and P=0.004, respectively). Among the 151 patients with low-grade UTUC, hydronephrosis was not associated with pathologic features and postoperative survival. CONCLUSIONS: Preoperative hydronephrosis was significantly associated with adverse pathologic features and postoperative survival in patients with high-grade UTUC.

2.
Food Chem ; 335: 127620, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32739810

RESUMO

A non-enzymatic browning reaction occurs easily in Dongbei Suancai (DS) during storage. Using the method of path analysis, the changes in contents of VC (ascorbic acid), polyphenol, reducing sugar, amino nitrogen, and 5-HMF (5-hydroxymethyl furfural) were investigated to analyze the direct pathways and determinants of browning caused by pre-production blanching at 100 °C (R-100), salt-addition increased from 2% to 6% (Y-6) and fermentation time extended from 30 d to 40 d (T-40), respectively. The results showed that R-100 could delay the browning by inhibiting two direct pathways of oxidative decomposition of VC and oxidation-polymerization of polyphenols, but T-40 could lead to an increase in degree of browning for which primary determinant was the interaction between polyphenol and reducing sugar, while Y-6 had no obvious effect on browning pathway and determinants. R-100 was thus deemed to be a good measure with inhibiting non-enzymatic browning in DS during storage.

3.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(8): 994-998, 2020 Aug 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33053544

RESUMO

The incidence of cervical cancer ranks the first among the gynecological malignant tumors. Given the implementation of widespread cervical cancer screening and the improvement of clinical treatment, the cervical cancer mortality has decreased substantially. However, surgery, radiotherapy, and chemotherapy may impair the ovarian function, resulting in premature ovarian insufficiency and premature climacteric, which has reduced the quality of life in young patients. As a new fertility preservation technology, autologous ovarian tissue cryopreservation and transplantation is developing rapidly and showing great potentiality in preserving ovarian endocrine function of young cervical cancer patients.


Assuntos
Preservação da Fertilidade , Neoplasias do Colo do Útero , Criopreservação , Detecção Precoce de Câncer , Feminino , Humanos , Qualidade de Vida
4.
Environ Sci Technol ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064464

RESUMO

The relative importance of common activities on indoor nitrous acid (HONO) mixing ratios was explored during high time resolution, month-long measurements by chemical ionization mass spectrometry in a previously unoccupied house. Indoor HONO varied from 0.2 to 84.0 ppb (mean: 5.5 ppb; median 3.8 ppb), an order of magnitude higher than simultaneously measured outdoor values, indicating important indoor sources. They agree well with simultaneous measurements of HONO by Laser-Photofragmentation/Laser-Induced Fluorescence. Before any combustion activities, the mixing ratio of 3.0 ± 0.3 ppb is indicative of secondary sources such as multiphase formation from NO2. Cooking (with propane gas), especially the use of an oven, led to significant enhancements up to 84 ppb, with elevated mixing ratios persisting for a few days due to slow desorption from indoor surface reservoirs. Floor bleach cleaning led to prolonged, substantial decreases of up to 71-90% due to reactive processes. Air conditioning modulated HONO mixing ratios driven by condensation to wet surfaces in the AC unit. Enhanced ventilation also significantly lowered mixing ratios. Other conditions including human occupancy, ozone addition, and cleaning with terpene, natural product, and vinegar cleaners had a much smaller influence on HONO background levels measured following these activities.

5.
J Inorg Biochem ; 212: 111208, 2020 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-33065383

RESUMO

Two new copper(II) complexes, 9-PMAH-Cu (1) and 9-FPMAH-Cu (2), of anthrahydrazone were synthesized and structurally characterized, in which 9-FPMAH (9-(4'-trifluoromethyl)-pyrimidine anthrahydrazone) is the 4'-CF3 derivative of 9-PMAH (9-pyrimidine anthrahydrazone). Both complexes 1 and 2 showed similar intercalative binding modes towards DNA and might compete with the typical DNA intercalator, GelRed, in the same binding site. They could also act as topoisomerase (type I) suppressor to effectively inhibit its activity, in which complex 1 was more effective than 2. The in vitro antitumor screening indicated that complex 1 displayed much higher antiproliferative ability than 2 and cisplatin towards all the tested tumor cell lines. On the other hand, complex 1 also showed high cytotoxicity against human normal liver cell line HL-7702, suggesting it is a potential high cytotoxic antitumor candidate. While it was also suggested that the loss of activity of complex 2 might be due to the presence of 4'-CF3 on the pyrimidine ring. Studies on the cellular level showed that complex 1 could arrest the cell cycle of the most sensitive T-24 cells at G2/M phase and induced cell apoptosis. Complex 1 further showed a significant suppression on the tumor growth on the T-24 tumor xenograft mouse model, but not reduced the body weight. Especially, complex 1 could retain its coordination state in H2O even in the presence of HSA. The results suggests that complex 1 is of enough safety to be considered as a promising anticancer candidate by combining the bioactive Cu(II) and the anthrahydrazone pharmacophore.

6.
Waste Manag Res ; : 734242X20962841, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028174

RESUMO

The unprecedented urbanization that is occurring worldwide brings with it a vast amount of solid waste, leading to a rapid increase in study of municipal waste management (MWM) worldwide. This mini-review assessed this body of research both quantitatively and qualitatively. The data for the review were 9711 publications indexed by the Science Citation Index Expanded and the Social Sciences Citation Index for the period 2000-2019. The analysis showed that developed countries, the United States in particular, led trends in research during the first part of the period, and developing countries made substantial contributions to the literature more recently. For all years since 2009 except for 2014, China produced more research than the United States, becoming the most productive country in the study of MWM. Home to five of the ten most productive global research institutes on this subject, China is also a hub for collaboration among countries and institutes, as is the United States. Using content analysis and keyword visualization, this study characterized two decades of study of MWM. This study found that the keywords "sustainability," "waste-to-energy," "life-cycle assessment," and "China" exhibited an upward trend in research. This study seeks the pathway to successful scientific research, helping guide researchers as they innovate in and contribute to the field, and proposes pathways that governments can take to build sustainable MWM systems.

7.
Hum Brain Mapp ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030796

RESUMO

Primary dysmenorrhea (PDM) is cyclic menstrual pain in the absence of pelvic anomalies, and it is thought to be a sex-hormone related disorder. Existing study has focused on the effects of menstrual cramps on brain function and structure, ignoring the psychological changes associated with menstrual pain. Here we examined whether pain empathy in PDM differs from healthy controls (HC) using task-based functional magnetic resonance imaging (fMRI). Fifty-seven PDM women and 53 matched HC were recruited, and data were collected at the luteal and menstruation phases, respectively. During fMRI scans, participants viewed pictures displaying exposure to painful situations and pictures without any pain cues and assessed the level of pain experienced by the person in the picture. Regarding the main effect of the pain pictures, our results showed that compared to viewing neutral pictures, viewing pain pictures caused significantly higher activation in the anterior insula (AI), anterior cingulate cortex, and the left inferior parietal lobule; and only the right AI exhibited a significant interaction effect (group × picture). Post-hoc analyses confirmed that, relative to neutral pictures, the right AI failed to be activated in PDM women viewing painsss pictures. Additionally, there was no significant interaction effect between the luteal and menstruation phases. It suggests that intermittent pain can lead to abnormal empathy in PDM women, which does not vary with the pain or pain-free phase. Our study may deepen the understanding of the relationship between recurrent spontaneous pain and empathy in a clinical disorder characterized by cyclic episodes of pain.

8.
Foot Ankle Int ; : 1071100720949861, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33040601

RESUMO

BACKGROUND: Osteochondral lesions of the talus (OLT) are relatively common. Following the failure of conservative treatment, many operative options have yielded varied results. In this study, midterm outcomes after fresh-frozen osteochondral allograft transplantation for the treatment of OLT were evaluated. METHODS: Twenty-five patients (12 women and 13 men) with a mean age 40.4 (range 18-70) years between 2009 and 2014 were enrolled. Of 25 ankles, 3, 13, 4, and 4 were involved with the talus at Raikin zone 3, 4, 6, and 7 as well as one coexisted with zone 4 and 6 lesion. The mean OLT area was 1.82 cm2 (range, 1.1-3.0). The mean follow-up period was 5.5 years (range, 4-9.3). Outcomes evaluation included the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, visual analog scale score, and 12-item Short Form Health Survey (SF-12). RESULT: AOFAS ankle-hindfoot score increased from 74 preoperatively to 94 at 2 years postoperatively (P < .001) and the SF-12 physical health component scores increased from 32 to 46 points (P < .001). Incorporation was inspected in all patients in the latest follow-up, and graft subsidence and radiolucency were observed in 2 and 7 cases, respectively, whereas graft collapse and revision OLT graft were not observed. Bone sclerosis was found in 6 of 25 patients. CONCLUSION: With respect to midterm results, fresh, frozen-stored allograft transplantation might be an option in the management of symptomatic OLT. LEVEL OF EVIDENCE: Level IV, retrospective case series.

9.
Cell Mol Biol (Noisy-le-grand) ; 66(6): 127-134, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33040798

RESUMO

Ankylosing spondylitis (AS) is a chronic, progressive, and inflammatory disease that mainly affects the central axis joint. Although this disease has already been well documented and studied, its pathogenesis is still not well understood. This study aimed to screen and identify key candidate genes involved in the progression of AS. For this purpose, expression profiles of GSE39340 and GSE41038 were downloaded from the Gene Expression Omnibus and displayed in the form of volcano plots and heatmaps. Differentially expressed genes (DEGs) were identified by the Limma package in R and functional enrichment analyses were performed. Moreover, STRING and Cytoscape were utilized to construct protein-protein interaction (PPI) networks and screen significant modules. Immunohistochemistry (IHC) in tissue chips of AS and normal human synovial tissues was performed to confirm the major proteins associated with its development. Western blotting (WB) and alizarin red staining were applied to validate the expression level of platelet-derived growth factor receptor beta (PDGFRB) and function during osteogenesis differentiation of fibroblasts in AS. A total of 256 DEGs were screened, including 191 up-regulated genes and 65 down-regulated genes. The enriched functions of these identified genes mainly included adherens junction, focal adhesion, and cell-substrate adherens junction. The pathways most highly associated with the progression of AS were TGF-ß signaling pathway, the Hippo signaling pathway, and the AGE-RAGE signaling pathway. In addition, IHC showed that mitogen-activated protein kinase 1 (MAPK1), C-X-C motif chemokine receptor 4 (CXCR4), and PDGFRB were highly expressed in AS. PDGFRB was found upregulated during osteogenesis of fibroblasts and stimulates osteogenesis in AS. These findings may improve our understanding of the molecular mechanisms controlling AS. Pharmacological targeting of PDGFRB may initiate a possible suppression of bone formation in AS.

10.
Mol Immunol ; 127: 212-222, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33011404

RESUMO

PURPOSE: Long noncoding RNAs (lncRNAs) have emerged as essential regulators in many biological processes; however, little is known about the role of lncRNAs in choroidal neovascularization (CNV). The aim of this study was to investigate the role of lncRNA NEAT1 in CNV formation, and assessed whether inhibition of lncRNA NEAT1 could suppress M2-type macrophage polarization and CNV. METHODS: The expression profiles of lncRNAs in a CNV mice model were accessed via microarray analysis. The role of lncRNA NEAT1 on macrophage polarization was assessed both in vitro and vivo. The interaction between lncRNA NEAT1, miR-148a-3p, and PTEN was assessed using a dual-luciferase reporter assay and RNA immunoprecipitation assay. Additionally, to evaluate the role of lncRNA NEAT1 on CNV development, eyes of mice in the mice CNV model were examined by Fluorescein Angiography (FA) and choroidal flatmounts on days 3 and 7 after intravitreal injection. RESULTS: The results revealed that 128 lncRNAs were significantly altered in the RPE-choroid-sclera complexes of CNV mice (P < 0.05, fold change > 2.0). Additionally, lncRNA NEAT1 increased in CNV formation and M2 macrophage polarization. LncRNA NEAT1 sponging miRNA-148a-3p targeting PTEN can modulate M2 macrophage polarization in mice CNV models as well as in bone marrow-derived macrophages cultured in vitro. Inhibition of lncRNA NEAT1 can suppress M2 macrophage both in vitro and vivo. Moreover, the intravitreal injection of a lncRNA NEAT1 Smart Silencer can inhibit CNV leakage and neovascularization. CONCLUSION: LncRNA NEAT1 via miRNA-148a-3p targeting PTEN plays a significant role in M2 macrophage polarization, while the inhibition of lncRNA NEAT1 can suppress choroidal neovascularization by inhibiting M2 macrophage polarization.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33042006

RESUMO

Introduction: Bariatric surgery is a well-received treatment for obesity with maximal weight loss at 12-36 months postoperatively. We investigated the effect of early bariatric surgery on weight reduction of Chinese patients in accordance with their preoperation characteristics. Materials and Methods: Altogether, 409 patients with obesity from a prospective cohort in a single bariatric center were enrolled retrospectively and evaluated for up to 4 years. Measurements obtained included surgery type, duration of diabetic condition, besides the usual body mass index data tuple. Weight reduction was expressed as percent total weight loss (%TWL) and percent excess weight loss (%EWL). Results: RYGB or SG were performed laparoscopically without mortality or complications. BMI generally plateaued at 12 months, having decreased at a mean of 8.78 kg/m2. Successful weight loss of >25% TWL was achieved by 35.16, 49.03, 39.22, 27.74, 20.83% of patients at 6, 12, 24, 36, and 48 months after surgery. Overall, 52.91% of our patients had lost 100% of their excess weight at 12 months, although there was a rather wide range among individuals. Similar variability was revealed in women of child-bearing age. Conclusion: Chinese patients undergoing bariatric surgery tend to achieve maximal weight loss and stabilization between 12 and 24 months postoperatively, instead of at >2 years. The finding of the shorter stabilization interval has importance to earlier intervention of weight loss related conditions and women's conception planning.

12.
Sci Rep ; 10(1): 16454, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020518

RESUMO

The pathophysiological differences between menstrually-related migraine (MRM) and pure menstrual migraine (PMM) are largely unclear. The aim of this study was to investigate the potential differences in brain structure and function between PMM and MRM. Forty-eight menstrual migraine patients (32 MRM; 16 PMM) were recruited for this study. Voxel-based morphometry (VBM) was applied on structural magnetic resonance imaging (sMRI), and the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) in resting state functional MRI (rsfMRI) were calculated. No significant between-group difference was observed in the grey matter volume (GMV). MRM patients exhibited lower ALFF values at the dorsolateral prefrontal cortex (DLPFC) and medial prefrontal cortex (mPFC) than PMM patients. Moreover, the MRM group showed significantly higher ReHo values in the DLPFC. Higher values in the mPFC were related to higher expression of calcitonin gene-associated peptide (CGRP) in the PMM group (r = 0.5, P = 0.048). Combined ALFF and ReHo analyses revealed significantly different spontaneous neural activity in the DLPFC and mPFC, between MRM and PMM patients, and ALFF values in the mPFC were positively correlated with CGRP expression, in the PMM group. This study enhances our understanding of the relationship between neural abnormalities and CGRP expression in individuals with PMM.

13.
Biomed Res Int ; 2020: 4918239, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029510

RESUMO

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by sacroiliitis and spinal rigidity of the axial joints. The role of oxidative stress and increased proinflammatory cytokines is well documented in AS pathogenesis. Punicalagin (2,3-hexahydroxydiphenoyl-gallagyl-D-glucose), an ellagitannin widely present in pomegranates, is found to exhibit potent anti-inflammatory, antiproliferative, and antioxidative effects. The present study was undertaken to investigate the effects of punicalagin in a rodent model of AS. Methods: BALB/c mice induced spondylitis were sacrificed 24 h after the last injection of proteoglycan extract. Histological scoring was done to assess the degree of the disease. The expression of JAK2/STAT3 proteins and proteins of the nuclear factor-κB (NF-κB) pathway was determined by immunoblotting. Serum levels of inflammatory mediators-TNF-α, IL-1ß, IL-6, IL-17A, and IL-23-were assessed. Levels of lipid peroxidation and reactive oxygen species (ROS) were quantified. Antioxidant status as a measure of activities of antioxidant enzymes-catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)-was determined. Results: Punicalagin effectively improved antioxidant status and decreased lipid peroxidation, ROS production, and serum levels of inflammatory mediators. NF-κB pathway and JAK2/STAT3 signaling were significantly (p < 0.05) downregulated. Punicalagin effectively regulated the production of cytokines by the Th17 cells and the IL-17A/IL-23 axis. Conclusion: The observations suggest that punicalagin exerts a protective role in AS via reducing oxidative stress and regulating NF-κB/TH17/JAK2/STAT3 signal. Punicalagin thus could be explored further as a potent candidate compound in the treatment of AS.

14.
Signal Transduct Target Ther ; 5(1): 214, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33033232

RESUMO

Epidermal growth factor receptor (EGFR) activation plays a pivotal role in EGFR-driven non-small cell lung cancer (NSCLC) and is considered as a key target of molecular targeted therapy. EGFR tyrosine kinase inhibitors (TKIs) have been canonically used in NSCLC treatment. However, prevalent innate and acquired resistances and EGFR kinase-independent pro-survival properties limit the clinical efficacy of EGFR TKIs. Therefore, the discovery of novel EGFR degraders is a promising approach towards improving therapeutic efficacy and overcoming drug resistance. Here, we identified a 23-hydroxybetulinic acid derivative, namely DPBA, as a novel EGFR small-molecule ligand. It exerted potent in vitro and in vivo anticancer activity in both EGFR wild type and mutant NSCLC by degrading EGFR. Mechanistic studies disclosed that DPBA binds to the EGFR extracellular domain at sites differing from those of EGF and EGFR. DPBA did not induce EGFR dimerization, phosphorylation, and ubiquitination, but it significantly promoted EGFR degradation and repressed downstream survival pathways. Further analyses showed that DPBA induced clathrin-independent EGFR endocytosis mediated by flotillin-dependent lipid rafts and unaffected by EGFR TKIs. Activation of the early and late endosome markers rab5 and rab7 but not the recycling endosome marker rab11 was involved in DPBA-induced EGFR lysosomal degradation. The present study offers a new EGFR ligand for EGFR pharmacological degradation and proposes it as a potential treatment for EGFR-positive NSCLC, particularly NSCLC with innate or acquired EGFR TKI resistance. DPBA can also serve as a chemical probe in the studies on EGFR trafficking and degradation.

15.
Pflugers Arch ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033891

RESUMO

Tacrolimus (TAC, also called FK506), a common immunosuppressive drug used to prevent allograft rejection in transplant patients, is well known to alter the functions of blood vessels. In this study, we sought to determine whether chronic treatment of TAC could inhibit the activity of big-conductance Ca2+-activated K+ (BK) channels in vascular smooth muscle cells (SMCs), leading to hypertension. Our data reveal that the activity of BK channels was inhibited in cerebral artery SMCs (CASMCs) from mice after intraperitoneal injection of TAC once a day for 4 weeks. The voltage sensitivity, Ca2+ sensitivity, and open time of single BK channels were all decreased. In support, BK channel ß1-, but not α-subunit protein expression was significantly decreased in cerebral arteries. In TAC-treated mice, application of norepinephrine induced stronger vasoconstriction in both cerebral and mesenteric arteries as well as a larger [Ca2+]i in CASMCs. Chronic treatment of TAC, similar to BK channel ß1-subunit knockout (KO), resulted in hypertension in mice, but did not cause a further increase in blood pressure in BK channel ß1-subunit KO mice. Moreover, BK channel activity in CASMCs was negatively correlated with blood pressure. Our findings provide novel evidence that TAC inhibits BK channels by reducing the channel ß1-subunit expression and functions in vascular SMCs, leading to enhanced vasoconstriction and hypertension.

16.
Biomed Chromatogr ; : e4998, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33037660

RESUMO

Isoliquiritigenin and isoliquiritin, two kinds of major flavonoids in licorice, are biological active substances with antioxidant, anti-inflammatory and tumor-suppressive effects. However, their in vivo metabolites, possible material basis of this two licorice chalcones for the diseases treatment, have not been fully studied. To clarify the metabolism of isoliquiritigenin and isoliquiritin, the metabolites of this two licorice chalcones in mice plasma, urine, feces and bile after oral administration of 100 mg/kg/d for consecutive 8 days were determined using liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry in this study. The structures of those metabolites were tentatively identified according to their fragment pathways, accurate masses, characteristic product ions, metabolism law and reference standards-matching. As a result, a total of 25 o 29 metabolites of isoliquiritigenin or isoliquiritin were respectively identified. Seven main metabolic pathways, including oxidation and reduction, deglycosylation and glycosylation, dehydroxylation and hydroxylation, demethoxylation and methoxylation, acetylation, glucuronidation and sulfation were summarized to tentatively explain how the metabolites were biologically transformed. These results provide the important information on the metabolism of isoliquiritigenin and isoliquiritin, which may be helpful for the further research of their pharmacological mechanism.

17.
Mol Ther ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-33007201

RESUMO

Follistatin-like 1 (FSTL1) is a matricellular protein that is upregulated during development and disease, including idiopathic pulmonary fibrosis (IPF), keloid, and arthritis. The profibrotic and pro-inflammatory roles of FSTL1 have been intensively studied during the last several years, as well as in this report. We screened and identified epitope-specific monoclonal neutralizing antibodies (nAbs) to functionally block FSTL1. FSTL1 nAbs attenuated bleomycin-induced pulmonary and dermal fibrosis in vivo and transforming growth factor (TGF)-ß1-induced dermal fibrosis ex vivo in human skin. In addition, FSTL1 nAbs significantly reduced existing lung fibrosis and skin fibrosis in experimental models. FSTL1 nAbs exerted their potent antifibrotic effects via reduced TGF-ß1 responsiveness and subsequent myofibroblast activation and extracellular matrix production. We also observed that FSTL1 nAbs attenuated the severity of collagen-induced arthritis in mice, which was accompanied by reduced inflammatory responses in vitro. Our findings suggest that FSTL1 nAbs are a promising new therapeutic strategy for the treatment of multiple organ fibrosis and systemic autoimmune diseases.

18.
J Clin Periodontol ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33010026

RESUMO

AIM: This systematic review and network meta-analysis aimed to evaluate the efficacy of adjunctive locally delivered antimicrobials, compared to subgingival instrumentation alone or plus a placebo, on changes in probing pocket depth (PPD) and clinical attachment level (CAL), in patients with residual pockets during supportive periodontal care. MATERIALS AND METHODS: Literature search was performed with electronic databases and by hand until May 31st , 2020. Primary outcome was the changes in PPD. The treatment effects between groups were estimated with weighted mean differences (WMD) with 95% confidence intervals (CI) and prediction intervals (PI) by using random-effects network meta-analysis. RESULTS: Twenty-two studies were included. Significantly greater PPD reduction was achieved in chlorhexidine chip group (WMD: 0.65mm, 95% CI: 0.21-1.10) and tetracycline fiber group (WMD: 0.64 mm, 95% CI: 0.20-1.08) over 6-month follow-up. Other adjunctive antimicrobial agents achieved non-significant improvements compared to scaling and root planing alone. All differences between adjunctive therapies were statistically non-significant. Similar findings were observed for CAL gain. CONCLUSION: Adjunctive local antimicrobial agents achieved small additional PPD reduction and CAL gain in residual pockets for a follow-up of up to 6 months. Tetracycline fiber and chlorhexidine chip achieved better results than other antimicrobials.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33020270

RESUMO

Understanding differences in DNA double-strand break (DSB) repair between tumor and normal tissues would provide a rationale for developing DNA repair-targeted cancer therapy. Here, using knock-in mouse models for measuring the efficiency of two DSB repair pathways, homologous recombination (HR) and nonhomologous end-joining (NHEJ), we demonstrated that both pathways are up-regulated in hepatocellular carcinoma (HCC) compared with adjacent normal tissues due to altered expression of DNA repair factors, including PARP1 and DNA-PKcs. Surprisingly, inhibiting PARP1 with olaparib abrogated HR repair in HCC. Mechanistically, inhibiting PARP1 suppressed the clearance of nucleosomes at DNA damage sites by blocking the recruitment of ALC1 to DSB sites, thereby inhibiting RPA2 and RAD51 recruitment. Importantly, combining olaparib with NU7441, a DNA-PKcs inhibitor that blocks NHEJ in HCC, synergistically suppressed HCC growth in both mice and HCC patient-derived-xenograft models. Our results suggest the combined inhibition of both HR and NHEJ as a potential therapy for HCC.

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